DESCRIPTION: The long range goal of this project is to determine whether androgen receptor (AR) mutations/polymorphisms can be used as a functional biomarker of prostate cancer development or progression. The applicant theorized that androgen independent tumors have escaped androgen control because the receptor has become functionally activated because of gene mutation. Her preliminary studies have shown that androgen receptor mutations frequently occur in advanced prostate cancer, the proposal seeks support to define whether androgen receptor mutations/polymorphisms can be used as a functional biomarker of prostate cancer development or progression by defining the incidence and type of mutations associated with prostate cancer. It is imperative that the functional significance of these mutations be defined. These studies will define the significance of androgen receptor mutations in the development/progression of prostate cancer and validate their application as biomarkers.